EU/3/12/973: Orphan designation for the treatment of mucopolysaccharidosis type VII (Sly syndrome)

Mucopolysaccharidosis type VII (also known as Sly syndrome) is an inherited disease caused by a lack of the enzyme beta-glucuronidase. This enzyme is needed to break down substances in the body called glycosaminoglycans (GAGs). If the enzyme is not present, GAGs cannot be broken down and they build up in the cells and damage them. This causes a wide range of problems such as short stature, skeletal abnormalities, joint stiffness, enlarged spleen and liver, lung infections, heart problems and hernias. Patients usually die within the first year of life, although some survive into their teenage years.

Mucopolysaccharidosis type VII is a life-threatening disease with many patients dying in early childhood. It also debilitating due to the physical and skeletal abnormalities that occur.

At the time of designation, mucopolysaccharidosis type VII affected approximately 0.001 in 10,000 people in the European Union (EU). This was equivalent to a total of around 50 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 512,200,000 (Eurostat 2013).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of mucopolysaccharidosis type VII. Bone marrow transplantation was sometimes used to treat the condition.

Recombinant human beta-glucuronidase is an enzyme replacement therapy that is expected to work by replacing the missing beta-glucuronidase enzyme in patients with mucopolysaccharidosis type VII. The medicine is produced by a method known as 'recombinant DNA technology', which involves inserting a gene into a cell, enabling the cell to make the enzyme.

At the time of submission of the application for orphan designation, the evaluation of the effects of recombinant human beta-glucuronidase in experimental models was ongoing.

At the time of submission, no clinical trials with recombinant human beta-glucuronidase in patients with mucopolysaccharidosis type VII had been started.

At the time of submission, recombinant human beta-glucuronidase was not authorised anywhere in the EU for mucopolysaccharidosis type VII or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 January 2012 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.